UNIT 6A Respiratory System 2024-2025 PDF

UNIT 6 ABSORPTION and EXCRETION  Contents PART 1 – The Respiratory System PART 2 – The Digestive System PART 3 – The Urinary System  Principles of Anatomy and Physiology 14th Edition CHAPTER 23 The Respiratory System  Un...

UNIT 6 ABSORPTION and EXCRETION  Contents PART 1 – The Respiratory System PART 2 – The Digestive System PART 3 – The Urinary System  Principles of Anatomy and Physiology 14th Edition CHAPTER 23 The Respiratory System  Unit Objectives o Identify and locate the structures that make up the respiratory system o Trace the path of air through the respiratory tree o Describe the structures and functions of the conducting and respiratory zones of the lungs. o Describe the location and significance of the pleural membranes o Summarize the physical principles controlling the movement of air into and out of the lungs, and describe the origins and actions of the muscles responsible for respiratory movements. o Explain how intrapleural and intrapulmonary pressures change during breathing.  Unit Objectives o Explain how lung compliance, elasticity, and surface tension affect breathing, and the significance of pulmonary surfactant. o Describe the exchange of oxygen and carbon dioxide in external and internal respiration. o Describe how the blood transports oxygen and carbon dioxide. o Describe the various conditions that influence the oxyhemoglobin dissociation curve and oxygen transport. o Explain how ventilation is regulated by the CNS.  Outline A. Functions of the Respiratory System B. Organs of the Respiratory System C. Mechanism of Breathing: Inhalation and Exhalation D. Pulmonary Volumes E. External (pulmonary) respiration F. Internal (tissue) respiration G. Respiratory gas transport H. Regulation of Respiration I. Pathophysiology  Facts About the Respiratory System The right lung is slightly larger than the left. Hairs in the nose help to clean the air we breathe as well as warming it. It is healthier to breathe through your nose than your mouth The surface area of the lungs is roughly the same size as a tennis court. The capillaries in the lungs would extend 1,600 kilometers if placed end to end.  More Facts About the Respiratory System We lose half a liter of water a day through breathing. This is the water vapor we see when we breathe onto a glass. A person at rest usually breathes between 12 and 15 times a minute. The breathing rate is faster in children and women than in men. The highest recorded "sneeze speed" is 165 km per hour. A. Major Functions of the Respiratory System Respiration – four distinct processes must happen – Pulmonary ventilation – moving air into and out of the lungs – External respiration – gas exchange between the lungs and the blood – Transport – transport of oxygen and carbon dioxide between the lungs and tissues – Internal respiration – gas exchange between systemic blood vessels and tissues A. Major Functions of the Respiratory System Gas exchange: Oxygen enters blood and carbon dioxide leaves Regulation of blood pH: Altered by changing blood carbon dioxide levels (increase CO2 = decrease pH) Voice production: Movement of air past vocal folds makes sound and speech Olfaction: Smell occurs when airborne molecules are drawn into nasal cavity Protection: Against microorganisms by preventing entry and removing them from respiratory surfaces.  B. Organs Of The Respiratory System Nose Pharynx Larynx Trachea Bronchi Lungs - alveoli Respiratory System STRUCTURAL Divisions Upper tract: nose, pharynx and associated structures Lower tract: larynx, trachea, bronchi, lungs and the tubing within the lungs  The Upper Respiratory Tract ◼ Passageway for respiration ◼ Receptors for smell ◼ Filters incoming air to filter larger foreign material ◼ Moistens and warms incoming air ◼ Resonating chambers for voice  The Lower Respiratory Tract ◼ Functions: ◼ Larynx: maintains an open airway, routes food and air appropriately, assists in sound production ◼ Trachea: transports air to and from lungs ◼ Bronchi: branch into lungs ◼ Lungs: transport air to alveoli for gas exchange  Respiratory System FUNCTIONAL Divisions Respiratory zone – Site of gas exchange – Consists of bronchioles, alveolar ducts, alveolar sacs and alveoli Conducting zone – Provides rigid conduits for air to reach the sites of gas exchange – Includes all other respiratory structures (e.g., nose, nasal cavity, pharynx, larynx, trachea, bronchi, bronchioles and terminal bronchioles) Respiratory muscles – diaphragm and other muscles that promote ventilation Muscles of Inhalation and Exhalation Structures of the Respiratory System  Cartilaginous Framework of the Nose The external portion of the nose is made of cartilage and skin and is lined with mucous membrane  Internal Anatomy of the Nose The bony framework of the nose is formed by the frontal, nasal, and maxillary bones Nasal Conchae and Meatuses  Surface Anatomy of the Nose 1. Root 2. Apex 3. Bridge 4. External naris  Paranasal Sinuses Cavities within bones Functions: surrounding the nasal 1. Lightens the skull cavity: Frontal Bone, 2. Acts as resonating Sphenoid Bone, chambers for speech Ethmoid Bone, Maxillary Bone 3. Produce mucus that drains the nasal cavity  Pharynx The pharynx functions as a passageway for air and food, provides a resonating chamber for speech sounds, and houses the tonsils, which participate in immunological reactions against foreign invaders  Larynx The larynx (voice box) is a passageway that connects the pharynx and trachea  Larynx The larynx contains vocal folds, which produce sound when they vibrate Structures of Voice Production  Trachea The trachea extends from the larynx to the primary bronchi Trachea  Bronchi At the superior border of the 5th thoracic vertebrae, the trachea branches into a right primary bronchus which enters the right lung and a left primary bronchus which enters the left lung  Bronchi Upon entering the lungs, the primary bronchi further divide to form smaller and smaller diameter branches – The terminal bronchioles are the end of the conducting zone  Lungs The lungs are paired organs in the thoracic cavity  Lungs The lungs are enclosed and protected by the pleural membrane Lobes and Fissures of the Lungs  Alveoli When the conducting zone ends at the terminal bronchioles, the respiratory zone begins The respiratory zone terminates at the alveoli, the “air sacs” found within the lungs Respiratory Zone  Alveoli in a Lobule of a Lung Alveoli represent the most distal portion of the respiratory tract. There are approximately 500 million alveoli in the human body.  Alveolus Each alveolus consists of three types of cell populations: Type I Pneumocytes Type II Pneumocytes Alveolar macrophages  Type I Pneumocytes Cover 70% of the internal surface of each alveolus. These cells are thin and squamous, ideal for gas exchange (main site). They share a basement membrane with pulmonary capillary endothelium, forming the air-blood barrier where gas exchange occurs.  Type I Pneumocytes Type I Pneumocytes have the following functions. 1.Facilitate gas exchange 2.Maintain ion and fluid balance within the alveoli 3.Communicate with type II pneumocytes to secrete surfactant in response to stretch. 4.Secrete Angiotensin Converting Enzyme (ACE) Angiotensin Converting Enzyme Angiotensin Converting Enzyme  Angiotensin Converting Enzyme ACE converts angiotensin I into angiotensin II, which are two important hormones in the renin- angiotensin feedback loop of the renal system. This system works to regulate blood pressure and blood volume by changing the amount of water retained by the kidneys. In general, more ACE leads to more angiotensin II, which leads to more aldosterone, which leads to more retained water through sodium reabsorption in the kidney, which leads to increased blood volume and blood pressure.  Type II Pneumocytes Cover 7% of the internal surface of each alveolus. These cells have a mean volume that is half that of the type I pneumocyte with apical microvilli. Within their cytoplasm are characteristic lamellar bodies containing a surfactant, a substance secreted that decreases the surface tension of alveoli. Though they occur more often, they are less involved in lining the alveolar surface.  Type II Pneumocytes Type II Pneumocytes have four main functions. 1. Produce and secrete pulmonary surfactant - surfactant is a vital substance that reduces surface tension, preventing alveoli from collapsing. 2. Expression of immunomodulatory proteins that are necessary for host defense 3. Transepithelial movement of water 4. Regeneration of alveolar epithelium after injury - At the time of injury, Type II cells are transformed into Type I cells.  Surfactant – Surface Active Agent – A substance added to liquid that reduces its surface tension, increasing its spreading – Lung surfactant is a complex with a unique phospholipid and protein composition. – Dipalmitoylphosphatidylcholine, and four surfactant-associated proteins, SP-A, SP-B, SP-C, and SP-D.  Functions of Surfactant – Reduces surface tension at the pulmonary air- liquid interface; Prevents atelectasis (collapse of lung) – Stabilizes alveoli which is necessary to withstand the collapsing tendency – Inflates the lung after birth (before birth lungs are solid and uninflated); prevents Respiratory Distress Syndrome – Defense within the lungs against infection and inflammation (SPA and SPD) Surfactant  Alveolar Macrophages Mononuclear phagocytes that are residents in alveoli. They derive from blood monocytes. Alveolar macrophages play an essential role in our immune system. They collect inhaled particles from the environment, such as coal, silica, and asbestos, and microbes, including viruses, bacteria, and fungi.  Respiratory Membrane The respiratory membrane is composed of: 1. A layer of Type I and Type II alveolar cells and associated alveolar macrophages that constitutes the alveolar wall 2. An epithelial basement membrane underlying the alveolar wall 3. A capillary basement membrane that is often fused to the epithelial basement membrane 4. The capillary endothelium Respiratory Membrane  Respiratory Membrane Gas exchanges occurs across the respiratory membrane – It is < 0.1 μm thick – Lends to very efficient diffusion – Oxygen enters the blood – Carbon dioxide enters the alveoli – Macrophages add protection – Surfactant coats gas-exposed alveolar surfaces It is the site of external respiration and diffusion of gases between the inhaled air and the blood – Occurs in the pulmonary capillaries  Blood Supply to the Lungs Blood enters the lungs via the pulmonary arteries (pulmonary circulation) and the bronchial arteries (systemic circulation) Blood exits the lungs via the pulmonary veins and the bronchial veins Respiration (Gas Exchange) Steps 1. Pulmonary ventilation/ breathing Inhalation and exhalation Exchange of air between atmosphere and alveoli 2. External (pulmonary) respiration Exchange of gases between alveoli and blood 3. Internal (tissue) respiration Exchange of gases between systemic capillaries and tissue cells Supplies cellular respiration (makes ATP) 4. Respiratory gas transport Transport of oxygen and carbon dioxide via the bloodstream  C. Mechanics of Breathing (Pulmonary Ventilation) Completely mechanical process Depends on VOLUME CHANGES in the thoracic cavity Volume changes lead to pressure changes, which lead to the flow of gases to equalize pressure – AIR PRESSURE DIFFERENCES DRIVE AIR FLOW Two phases: Inspiration – flow of air into lung Expiration – air leaving lung  Boyle’s Law – The volume of a gas varies inversely with its pressure Position of the Diaphragm During Inhalation and Exhalation  Inhalation/ Inspiration – Pressure inside alveoli must become lower than atmospheric pressure for air to flow into lungs 760 millimeters of mercury (mmHg) or 1 atmosphere (1 atm) – Achieved by increasing size of lungs Boyle’s Law – pressure of a gas in a closed container is inversely proportional to the volume of the container – Inhalation – lungs must expand, increasing lung volume, decreasing pressure below atmospheric pressure  Inspiration Inhalation is active – Contraction of – Diaphragm – most important muscle of inhalation Flattens, lowering dome when contracted Responsible for 75% of air entering lungs during normal quiet breathing – External intercostals Contraction elevates ribs 25% of air entering lungs during normal quiet breathing Accessory muscles for deep, forceful inhalation  Inspiration When thorax expands, parietal and visceral pleurae adhere tightly due to subatmospheric pressure and surface tension As a result of this, the visceral pleura is “sucked” outwards bringing the walls of the lungs with it and causing the lungs to increase in volume (pulled along with expanding thorax) This draws air into the lungs from the atmosphere. Surface tension – Holds the pleural membranes together, which assists with lung expansion – Surfactant reduces surface tension within the alveoli Inspiration  Expiration – Pressure in lungs greater than atmospheric pressure – Normally passive – muscle relax instead of contract Diaphragm relaxes and become dome shaped External intercostals relax and ribs drop down Parietal pleura moves inwards with the chest wall, presses on the pleural cavity which creates a rise in intrapleural pressure. This slackens the outward pull on the visceral pleura which enables elastin fibers in the lung tissue to recoil. As a result, the lungs decrease in volume, pushing air out into the atmosphere as they do so. Expiration Pressure Changes in Pulmonary Ventilation Muscles of Breathing Muscles of Inhalation and Exhalation Muscles of Breathing - Inspiration Quiet Breathing Muscles include: – External intercostals – Diaphragm Contract to expand the rib cage and stretch the lungs = ↑ volume of the thoracic cavity ↑ intrapulmonary volume ↓ intrapulmonary pressure (relative to atmospheric pressure) Decreased pressure inside the lungs pulls air into the lungs down its pressure gradient until intrapulmonary pressure equals atmospheric pressure  Muscles of Breathing - Inspiration Forced or Deep Inspiration Involves several accessory muscles: – Sternocleidomastoid – Pectoralis minor – Scalenes (neck muscles) Maximal ↑ in thoracic volume Greater ↓ in intrapulmonary pressure More air moves into the lungs At the end of inspiration, the intrapulmonary pressure equals atmospheric pressure  Muscles of Breathing - Expiration Quiet Breathing Passive process – Depends on the elasticity of the lungs Muscles of inspiration relax – The rib cage descends – The lungs recoil ↓ intrapulmonary volume ↑ intrapulmonary pressure Alveoli are compressed, thus forcing air out of the lungs  Muscles of Breathing - Expiration Forced Expiration It is an active process – Occurs in activities such as blowing up a balloon, exercising, or yelling Abdominal wall muscles are involved in forced expiration – Function to ↑ the pressure in the abdominal cavity forcing the abdominal organs upward against the diaphragm ↓ volume of the thoracic cavity ↑ pressure in the thoracic cavity Air is forced out of the lungs Factors Affecting Pulmonary Ventilation (1) Air pressure differences drive airflow (2) Surface tension of alveolar fluid – Inwardly directed force in the alveoli which must be overcome to expand the lungs during each inspiration – Causes alveoli to assume smallest possible diameter – Accounts for 2/3 of lung elastic recoil – Due to intermolecular attractions between water molecules (water molecules become closer) Surface Tension Water molecules in the deeper layers are attracted from all sides. Water molecules in the surface are not attracted equally because of the presence of air on the surface Water molecules do not interact with air molecules causing surface tension  Laplace Law When the surface tension increases, the collapsing pressure increases and alveoli collapse. When the surface tension decreases, the collapsing pressure decreases and alveoli will expand  Surface Tension Type II alveolar epithelial cells secrete pulmonary surfactant to lower the surface tension of water, which helps prevent airway collapse. Reinflation of the alveoli following exhalation is made easier by pulmonary surfactant. Factors Affecting Pulmonary Ventilation (3) Lung compliance The ability of the lungs to be expanded, stretched, or inflated The ease with which the lungs can expand and contract in response to changes in pressure A measurement of the lung’s ability to stretch High lung compliance – easier to fill with air Low lung compliance – more difficult to fill with air Factors Affecting Pulmonary Ventilation (3) Lung compliance Two factors affecting lung compliance: surface tension of the alveoli and elasticity of lung tissue (mainly) – Due to collagen and elastin fibers interwoven within the lung parenchyma Factors Affecting Pulmonary Ventilation (3) Lung compliance – Elasticity refers to the ability of the lung to recoil to its original shape and size after it has been stretched or compressed – Due to elastic fibers that allow it to stretch and recoil back to its original shape and size. – Without elasticity, lungs will not be able to expel air during exhalation and would be unable to fill with air during inhalation Factors Affecting Pulmonary Ventilation (3) Lung compliance – In normal lungs there is a balance between compliance and elasticity – Recoil pressure is inversely proportional to compliance Increased compliance results in decreased recoil Decreased compliance results in increased recoil  High Lung Compliance A high lung compliance means that the lungs are too pliable and can expand and contract easily They have a lower-than-normal level of elastic recoil. This indicates that little pressure difference in pleural pressure is needed to change the volume of the lungs. Exhalation of air also becomes much more difficult because the loss of elastic recoil reduces the passive ability of the lungs to deflate during exhalation.  High Lung Compliance High lung compliance is commonly seen in those with obstructive diseases, such of emphysema, in which destruction of the elastic tissue of the lungs from cigarette smoke exposure causes a loss of elastic recoil of the lung. Those with emphysema have considerable difficulty with exhaling breaths and tend to take fast shallow breaths and tend to sit in a hunched-over position in order to make exhalation easier. Their alveolar sacs have a high residual volume, which in turn causes difficulty in exhaling the excess air out of the lung, and patients develop shortness of breath. Emphysema Emphysema  Low Lung Compliance A low lung compliance means that the lungs are “stiff” and have a higher-than-normal level of elastic recoil. A stiff lung would need a greater-than-average change in pleural pressure to change the volume of the lungs, and breathing becomes more difficult as a result.  Low Lung Compliance Low lung compliance is commonly seen in people with restrictive lung diseases, such as pulmonary fibrosis, in which scar tissue deposits in the lung Lung elastin fibers are replaced by collagens, which are less elastic and decrease the compliance of lung making it much more difficult for the lungs to expand and gas exchange is impaired. Such patients need higher work of breathing to inflate more rigid lung alveoli. Pulmonary Fibrosis Pulmonary Fibrosis Factors Affecting Pulmonary Ventilation (4) Airway Resistance Airway resistance is the resistance/opposition to flow of air caused by friction with the airways, which includes the conducting zone for air, such as the trachea, bronchi and bronchioles. The main determinants of airway resistance are the size of the airway and the properties of the flow of air itself. Resistance and air flow are inversely related – ↑ airway resistance = ↓ air flow (and vice versa)  AIRWAY RESISTANCE Airway resistance is most affected by changes in the diameter of the bronchioles and smooth muscle tone; larger diameter has less resistance – ↓ diameter of the bronchioles = ↑ airway resistance  AIRWAY RESISTANCE Examples: – Asthma – Bronchospasm during an allergic reaction A high resistance to air flow produces a greater energy cost of breathing Epinephrine release via the sympathetic nervous system dilates bronchioles and reduces air resistance  Pathologic airway changes induced in asthma Mucous gland hypertrophy Epithelial damage Airway smooth Edema muscle Inflammatory cell infiltration Mucus Thickening of Vascular basement dilatation membrane Acute Reaction to Triggers 1. Irritated airways become more inflamed after exposure to stimuli 2. Muscle layers around airway constrict 3. Airway lining swells 4. Excess mucus builds up in lumen 5. Result: symptoms of cough, wheeze, shortness of breath, chest tightness Breathing Patterns and Respiratory Movements  Non-Respiratory Air Movements Can be caused by reflexes or voluntary actions Examples Cough and sneeze – clears lungs of debris Laughing Crying Yawn Hiccup D. Spirogram of Lung Volumes and Capacities  Lung Volumes and Capacities Minute ventilation (MV) = total volume of air inhaled and exhaled each minute Normal healthy adult averages 12 breaths per minute Factors affecting respiratory capacity – a person’s size, sex, age, physical condition moving about 500 ml of air in and out of lungs (tidal volume) MV = 12 breaths/min x 500 ml/ breath = 6 liters/ min  Lung Volumes Only about 70% of tidal volume reaches respiratory zone Other 30% remains in conducting zone Anatomic (respiratory) dead space – conducting airways with air that does not undergo respiratory gas exchange Alveolar ventilation rate – volume of air per minute that actually reaches respiratory zone  Lung Volumes Inspiratory reserve volume (IRV) Amount of air that can be taken in forcibly over the tidal volume Usually between 2100 and 3200 ml (Ave = 3100 ml) Expiratory reserve volume (ERV) Amount of air that can be forcibly exhaled Approximately 1200 ml  Lung Volumes Residual volume Air remaining in lung after expiration About 1200 ml Respiratory Capacities  Respiratory Capacities Vital capacity The total amount of exchangeable air Vital capacity = TV + IRV + ERV Total Lung Capacity Vital capacity + Residual Volume Respiratory Capacities  Respiratory Volumes and Capacities Functional volume Air that actually reaches the respiratory zone Usually about 350 ml Dead space volume Air that remains in conducting zone and never reaches alveoli About 150 ml  Respiratory Sounds Sounds are monitored with a stethoscope Bronchial sounds – produced by air rushing through trachea and bronchi Vesicular breathing sounds – soft sounds of air filling alveoli Bronchovesicular Respiratory Sounds Abnormal Respiratory Sounds Respiration (Gas Exchange) Steps 1. Pulmonary ventilation/ breathing Inhalation and exhalation Exchange of air between atmosphere and alveoli 2. External (pulmonary) respiration Exchange of gases between alveoli and blood 3. Internal (tissue) respiration Exchange of gases between systemic capillaries and tissue cells Supplies cellular respiration (makes ATP) 4. Respiratory gas transport Transport of oxygen and carbon dioxide via the bloodstream  E. Exchange of Oxygen and Carbon Dioxide – Dalton’s Law Dalton’s Law – Each gas in a mixture of gases exerts its own pressure as if no other gases were present – Pressure of a specific gas is partial pressure Px – Total pressure is the sum of all the partial pressures – Atmospheric pressure (760 mmHg) = PN2 + PO2 + PH2O + PCO2 + Pother gases – Each gas diffuses across a permeable membrane from the are where its partial pressure is greater to the area where its partial pressure is less – The greater the difference, the faster the rate of diffusion  Partial Pressures of Gases in Inhaled Air PN2 =0.786 x 760mm Hg = 597.4 mmHg PO2 =0.209 x 760mm Hg = 158.8 mmHg PH2O =0.004 x 760mm Hg = 3.0 mmHg PCO2 =0.0004 x 760mm Hg = 0.3 mmHg Pother gases =0.0006 x 760mm Hg = 0.5 mmHg TOTAL = 760.0 mmHg Exchange of Oxygen and Carbon Dioxide Because gases flow from areas of high pressure to areas of low pressure, atmospheric air has higher partial pressure of oxygen than alveolar air (PO2= 159mm Hg compared to PAO2= 100mm Hg). Similarly, atmospheric air has a much lower partial pressure for carbon dioxide compared to alveolar air (PCO2=.3mm Hg compared to PACO2= 40mm Hg). These pressure differences explain why oxygen flows into the alveoli and why carbon dioxide flows out of the alveoli through passive diffusion (just as a similar process explains alveolar and arterial gas exchange).  Henry’s Law Quantity of a gas that will dissolve in a liquid is proportional to the partial pressures of the gas and its solubility At a constant temperature, the amount of a given gas that dissolves in a given type and volume of liquid is directly proportional to the partial pressure of that gas in equilibrium with that liquid. Higher partial pressure of a gas over a liquid and higher solubility, more of the gas will stay in solution Gases with a higher solubility will have more dissolved molecules than gases with a lower solubility if they have the same partial pressure.  Henry’s Law The main application of Henry’s law in respiratory physiology is to predict how gases will dissolve in the alveoli and bloodstream during gas exchange. The amount of oxygen that dissolves into the bloodstream is directly proportional to the partial pressure of oxygen in alveolar air. The partial pressure of oxygen is greater in alveolar air than in deoxygenated blood, so oxygen has a high tendency to dissolve into deoxygenated blood. Conversely the opposite is true for carbon dioxide, which has a greater partial pressure in deoxygenated blood than in the alveolar air, so it will diffuse out of the solution and back into gaseous form.  External Respiration Oxygen movement into the blood The alveoli always has more oxygen than the blood Oxygen moves by diffusion towards the area of lower concentration Pulmonary capillary blood gains oxygen  External Respiration Carbon dioxide movement out of the blood Blood returning from tissues has higher concentrations of carbon dioxide than air in the alveoli Pulmonary capillary blood gives up carbon dioxide Blood leaving the lungs is oxygen-rich and carbon dioxide-poor Respiration (Gas Exchange) Steps 1. Pulmonary ventilation/ breathing Inhalation and exhalation Exchange of air between atmosphere and alveoli 2. External (pulmonary) respiration Exchange of gases between alveoli and blood 3. Internal (tissue) respiration Exchange of gases between systemic capillaries and tissue cells Supplies cellular respiration (makes ATP) 4. Respiratory gas transport Transport of oxygen and carbon dioxide via the bloodstream  Internal Respiration Cellular respiration is the metabolic process by which an organism obtains energy by reacting oxygen with glucose to give water, carbon dioxide, and adenosine triphosphate (energy). The 3 steps of cellular respiration are glycolysis, the Krebs cycle, and oxidative phosphorylation. Carbon dioxide is a waste product of cellular respiration that comes from the carbon in glucose and the oxygen used in cellular respiration.  Internal Respiration Internal respiration involves gas exchange between the bloodstream and tissues, and cellular respiration. An opposite reaction to what occurs in the lungs Carbon dioxide diffuses out of tissue to blood Oxygen diffuses from blood into tissue Internal Respiration  Internal Respiration Internal respiration – in tissues throughout body Oxygen – Oxygen diffuses from systemic capillary blood (PO2 100 mmHg) into tissue cells (PO2 40 mmHg) – cells constantly use oxygen to make ATP – Blood drops to 40 mmHg by the time blood exits the systemic capillaries Carbon dioxide – Carbon dioxide diffuses from tissue cells (PCO2 45 mmHg) into systemic capillaries (PCO2 40 mmHg) – cells constantly make carbon dioxide – PCO2 blood reaches 45 mmHg At rest, only about 25% of the available oxygen is used – Deoxygenated blood would retain 75% of its oxygen capacity  Rate of Pulmonary and Systemic Gas Exchange Depends on – Partial pressures of gases Alveolar PO2 must be higher than blood PO2 for diffusion to occur – problem with increasing altitude – Surface area available for gas exchange – Diffusion distance – Molecular weight and solubility of gases O2 has a lower molecular weight and should diffuse faster than CO2 except for its low solubility - when diffusion is slow, hypoxia occurs before hypercapnia Copyright 2009, John Wiley & Sons, Inc. Copyright 2009, John Wiley & Sons, Inc. Respiration (Gas Exchange) Steps 1. Pulmonary ventilation/ breathing Inhalation and exhalation Exchange of air between atmosphere and alveoli 2. External (pulmonary) respiration Exchange of gases between alveoli and blood 3. Internal (tissue) respiration Exchange of gases between systemic capillaries and tissue cells Supplies cellular respiration (makes ATP) 4. Respiratory gas transport Transport of oxygen and carbon dioxide via the bloodstream  G. Gas Transport In The Blood Oxygen transport – Only about 1.5% dissolved in plasma – 98.5% bound to hemoglobin in red blood cells Oxygen binding capacity between 1.36 and 1.37 ml O2 per gram Hgb. There are roughly 270 million hemoglobin molecules in a single red blood cell Heme portion of hemoglobin contains 4 iron atoms – each can bind one O2 molecule Oxyhemoglobin Only dissolved portion can diffuse out of blood into cells Oxygen must be able to bind and dissociate from heme Gas Transport In The Blood  Hemoglobin and Oxygen Several factors affecting affinity of Hemoglobin for oxygen Each makes sense if you keep in mind that metabolically active tissues need O2, and produce acids, CO2, and heat as wastes Factors Affecting the Affinity of Hb for O2 PO2 pH Temperature Type of Hb Carbon monoxide exposure - Carbon monoxide binds to hemoglobin in place of oxygen, so that less oxygen reaches the tissues  Relationship between Hemoglobin and Oxygen Partial Pressure The percentage of oxygen that is saturated in the hemoglobin of blood is generally represented by a curve that shows the relationship between PaO2 and O2 saturation. Saturation of O2 in hemoglobin is an indicator for how much O2 is able to reach the tissues of the body. Higher PaO2 means higher saturation of oxygen in blood. Fully saturated – completely converted to oxyhemoglobin Oxygen-hemoglobin Dissociation Curve  Oxygen-hemoglobin Dissociation Curve The lower areas of the curve show saturation when oxygen is unloaded into the tissues. The curve starts to plateau at PaO2 higher than 60 mmHG, meaning that increases in PaO2 after that point won’t significantly increase saturation. This also means that the approximate carrying capacity for oxygen in hemoglobin has been reached and excess oxygen won’t go into hemoglobin. The carrying capacity can be increased if more hemoglobin is added to the system, such as through greater red blood cell generation in high altitude, or from blood transfusions. Figure 18.4b  Hemoglobin States – Deoxyhemoglobin – tense state; very difficult for oxygen to gain access to the iron-binding sites – Oxyhemoglobin – relaxed state; – Cooperative binding - easy for hemoglobin to bind; once an oxygen binds to one site, iron moves slightly and so do parts of the peptide chains attached to it, making it easier for the next oxygen to bind until all 4 sites are occupied by oxygen  Oxygen-hemoglobin Dissociation Curve The oxyhemoglobin dissociation curve can shift in response to a variety of factors. Shifts indicate a change in affinity for oxygen’s binding to hemoglobin, which changes the ability of oxygen to bind to hemoglobin and stay bound to it (i.e., not be released from it). Rightward shifts indicate a decreased affinity for the binding of hemoglobin, so that less oxygen binds to hemoglobin, and more oxygen is unloaded from it into the tissues. Leftward shifts indicate an increased affinity for the binding of hemoglobin, so that more oxygen binds to hemoglobin, but less oxygen is unloaded from it into the tissues. Oxygen-hemoglobin Dissociation Curve Oxygen-hemoglobin Dissociation Curve MNEMONICS CADET, face right! Factors leading to a Right Shift – increase factors, increase shift to the right PCO2 Acid, 2,3-Diphosphoglycerate Exercise Temperature  pH Changes (Bohr Effect) – As acidity increases (pH decreases), affinity of Hb for O2 decreases – Increasing acidity enhances unloading – Shifts curve to right PCO2 – Also shifts curve to right – As PCO2 rises, Hb unloads oxygen more easily – Low blood pH can result from high PCO2  2,3 Bisphosphoglycerate Formerly named 2,3-diphosphoglycerate or 2,3-DPG BPG formed by red blood cells during glycolysis Easier oxygen unloading in the peripheral tissue In the absence of 2,3-BPG, hemoglobin's affinity for oxygen increases. High levels of 2,3-BPG shift the curve to the right (as in childhood) Low levels of 2,3-BPG cause a leftward shift (septic shock)  Temperature Changes – Within limits, as temperature increases, more oxygen is released from Hb – During hypothermia, more oxygen remains bound  Fetal and Maternal Hemoglobin Fetal hemoglobin has a higher affinity for oxygen than adult hemoglobin Hb-F can carry up to 30% more oxygen Maternal blood’s oxygen readily transferred to fetal blood  Carbon Dioxide Transport – Dissolved CO2 Smallest amount, about 7% – Carbamino compounds About 23% combines with amino acids including those in Hb Carbaminohemoglobin – Bicarbonate ions 70% transported in plasma as HCO3- Enzyme carbonic anhydrase forms carbonic acid (H2CO3) which dissociates into H+ and HCO3- Carbon Dioxide Transport – Dissolved Carbon Dioxide CO2 molecules that aren’t bound to anything else. Carbon dioxide has a much higher solubility than oxygen, which explains why a relatively greater amount of carbon dioxide is dissolved in the plasma compared to oxygen. Carbon Dioxide Transport – Bound to Hemoglobin While oxygen binds to the iron content in the heme of hemoglobin, carbon dioxide can bind to the amino acid chains on hemoglobin. When carbon dioxide clings to hemoglobin it forms carbanimohemoglobin. Carbanimohemoglobin gives red blood cells a bluish color, which is one of the reasons why the veins that carry deoxygenated blood appear to be blue.  Carbon Dioxide Transport – Bound to Hemoglobin Haldane Effect - deoxygenated blood has an increased capacity to carry carbon dioxide, while oxygenated blood has a decreased capacity to carry carbon dioxide. This property means that hemoglobin will primarily carry oxygen in systemic circulation until it unloads that oxygen and is able to carry a relatively higher amount of carbon dioxide. This is due to deoxygenated blood’s increased capacity to carry carbon dioxide, and from the carbon dioxide loaded from the tissues during tissue gas exchange.  Carbon Dioxide Transport – Bicarbonate Ions CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3- Implication: The pH of blood becomes a way of determining the amount of carbon dioxide in blood. This is because if carbon dioxide increases in the body, it will manifest as increased concentrations of bicarbonate and increased concentrations of hydrogen ions that reduce blood pH and make the blood more acidic.  Carbon Dioxide Transport – Bicarbonate Ions CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3- Implication: If carbon dioxide levels are reduced, there will be less bicarbonate and less hydrogen ions dissolved in the blood, so pH will increase and blood will become more basic. Bicarbonate ions act as a buffer for the pH of blood so that blood pH will be neutral as long as bicarbonate and hydrogen ions are balanced.  Carbon Dioxide Transport – Bicarbonate Ions CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3- This connection explains how ventilation rate and blood chemistry are related, as hyperventilation will cause alkalosis, and hypoventilation will cause acidosis, due to the changes in carbon dioxide levels that they cause. External Respiration, Gas Transport, and Internal Respiration Summary Figure 13.10  H. Regulation of Respiration Normally, quiet, regular breathing occurs because of two regulatory mechanisms: Neural or Nervous Regulation Chemical Regulation  Neural Regulation of Respiration Involves respiratory centers, afferent and efferent nerves. Respiratory centers: In the medulla oblongata and pons that collects sensory information about the level of oxygen and carbon dioxide in the blood and determines the signals to be sent to the respiratory muscles. Stimulation of these respiratory muscles provide respiratory movements which leads to alveolar ventilation.  Neural Regulation of Respiration Respiratory centers are group of neurons, which control the rate, rhythm and force of respiration. Respiratory centers are situated bilaterally in the reticular formation of the brainstem Respiratory centers are classified into two groups: 1. Medullary centers – control rate and depth of respiration 2. Pontine centers- smooths out respiratory rate  Respiratory Centers A. Medullary centers: 1. Dorsal respiratory group of neurons 2. Ventral respiratory group of neurons B. Pontine centers: 3. Apneustic center 4. Pneumotaxic center Respiratory Centers  Dorsal Respiratory Group of Neurons Diffusely situated in the nucleus of tractus solitarius (NTS) which is present in the upper part of the medulla oblongata. Usually, these neurons are collectively called inspiratory center. All the neurons of dorsal respiratory group are inspiratory neurons and generate inspiratory ramp by the virtue of their autorhythmic property. Function: Dorsal group of neurons are responsible for basic rhythm of respiration. Ventral Respiratory Group of Neurons Present in nucleus ambiguous and nucleus retroambiguous Situated in the medulla oblongata, anterior and lateral to the nucleus of tractus solitarius Earlier, called expiratory center but has both inspiratory and expiratory neurons Function: Normally inactive during quiet breathing and become active during forced breathing. During forced breathing, these neurons stimulate both inspiratory muscles and expiratory muscles. Medulla - Control of Respiration  Apneustic Center Situated in the reticular formation of lower pons Function: Increases depth of inspiration by acting directly on dorsal group neurons  Pneumotaxic Center Situated in the dorsolateral part of reticular formation in upper pons. Formed by neurons of medial parabrachial and subparabrachial nuclei. Subparabrachial nucleus is also called ventral parabrachial or Kölliker-Fuse nucleus.  Pneumotaxic Center Function: Primary function of pneumotaxic center is to control the medullary respiratory centers, particularly the dorsal group neurons. Pneumotaxic center inhibits the apneustic center so that the dorsal group neurons are inhibited. Because of this, inspiration stops and expiration starts. Thus, pneumotaxic center influences the switching between inspiration and expiration. Pneumotaxic center increases respiratory rate by reducing the duration of inspiration.  Central Chemoreceptors Located in the brain Central chemoreceptors are situated in the deeper part of medulla oblongata, close to the dorsal respiratory group of neurons. This area is known as chemosensitive area and the neurons are called chemoreceptors. Chemoreceptors are in close contact with blood and cerebrospinal fluid.  Central Chemoreceptors Mechanism of Action: They are very sensitive to increase in hydrogen ion concentration. Hydrogen ion cannot cross the blood brain barrier and blood cerebrospinal fluid barrier. On the other hand if carbon dioxide increases in the blood as it is a gas it can cross both the barrier easily and after entering the brain it combines with water to form carbonic acid.  Central Chemoreceptors As carbonic acid is unstable, it immediately dissociates into hydrogen and bicarbonate ions. The hydrogen ion now stimulates the central chemoreceptors which stimulates dorsal group of respiratory center (inspiratory group) and increase rate and force of breathing.  Peripheral Chemoreceptors Located in the carotid and aortic region Hypoxia Closure of oxygen sensitive potassium channels in the glomus cells of peripheral chemoreceptors Prevents potassium efflux Depolarization of glomus cells (receptor potential) and generation of action potentials in nerve ending. Excite the dorsal group of neurons.  Peripheral Chemoreceptors DGN send excitatory impulses to respiratory muscles, resulting in increased ventilation. In addition to hypoxia, peripheral chemoreceptors are also stimulated by hypercapnea and increased hydrogen ion concentration. However, the sensitivity of peripheral chemoreceptors to hypercapnea and increased hydrogen ion concentration is mild. Peripheral Chemoreceptors They are very sensitive to reduction in partial pressure of oxygen. Whenever, the partial pressure of oxygen decreases these chemoreceptors become activated and send impulses to inspiratory center and stimulate them. Thereby increases rate and force of respiration and rectifies the lack of oxygen. Control of Respiration  Factors Influencing Respiratory Rate and Depth Physical factors Increased body temperature Exercise Talking Coughing Volition (conscious control) Emotional factors  Factors Influencing Respiratory Rate and Depth Chemical factors Carbon dioxide levels Level of carbon dioxide in the blood is the main regulatory chemical for respiration Increased carbon dioxide increases respiration Changes in carbon dioxide act directly on the medulla oblongata  Factors Influencing Respiratory Rate and Depth Chemical factors (continued) Oxygen levels Changes in oxygen concentration in the blood are detected by chemoreceptors in the aorta and carotid artery Information is sent to the medulla oblongata  Control of Respiration Hypercapnia – A slight increase in PCO2 (and thus H+) – Stimulates central chemoreceptors Hypoxia – Oxygen deficiency at the tissue level – Caused by a low PO2 in arterial blood due to high altitude, airway obstruction or fluid in the lungs Copyright © 2014 John Wiley & Sons, Inc. 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